Interactions between Phospholipids and Organic Phases: Insights into Lipoproteins and Nanoemulsions

Abstract

The adsorption of phosphatidylcholines (PCs), dissolved in squalene or squalane as an organic phase, was studied at the interface with water. Using profile analysis tensiometry, the equilibrium adsorption isotherms, minimum molecular interfacial areas, and solubility limits were derived. For squalene, differences in PC solubility and interfacial adsorption were found, depending on PC saturation. Compared to saturated PCs, unsaturated PCs showed a 3-fold-lower interfacial density but up to a 28-fold-higher critical aggregation concentration (CAC). In addition, the solubility limit of unsaturated PC in squalene and in its saturated form squalane diverged by a factor of 739. These findings provided evidence for steric repulsion or π-π interactions of π bonds in both solvent and solute or both effects acting complementarily. In squalane, low solubilities but high interfacial densities were found for all investigated PCs. Changes in fatty acid chain lengths showed that the influence of the increases in entropy and enthalpy on solubility is much smaller than solvent/solute interactions. Oxidation products of squalene lowered the interfacial tension, but increasing concentrations of PC expelled them from the interface. The CAC of saturated PC was increased by oxidation products of squalene whereas that of unsaturated PCs was not. Our findings indicate that the oxidation of triglycerides in lipoprotein cores can lead to increased solubility of saturated phospholipids covering the lipoproteins, contributing to destabilization, coalescence, and terminally the formation of atherosclerotic plaques. The consideration of solvent/solute interactions in molecular modeling may contribute to the interfacial tension and the corresponding kinetic or thermodynamic stability of lipoproteins. Measured areas per molecule prove that PCs form monolayers of different interfacial densities at the squalene/water interface but multilayers at the squalane/water interface. These findings showed that combinations of solvent or solute saturation affect the outcome for nanoemulsions forming either expanded or condensed monolayers or multilayers.

Adsorption process for phospholipids of different chain lengths at a fluorocarbon/water interface studied by Du Noüy ring and spinning drop

“…Interfacial tensions are commonly measured with optical methods. Profile analysis tensiometry (PAT) has been used extensively to determine the adsorption process of surfactants [20][21][22] and is considered as non-invasive. The Du Noüy ring is one of the first established methods that allowed interfacial measurements [23].…”

Liposomes with asymmetric bilayers produced from inverse emulsions for nucleic acid delivery

“…In the case of DPPC/DSPE-PEG 2000 , we found that it takes approximately two hours to obtain a visible white thin layer ( Figure 2). However, we might also speculate that this 'thin layer' can be composed of multiple layers mainly composed of DPPC, as demonstrated by tensiometric measurements at oil-water interfaces by Hildebrandt et al [25,30].…”

“…Nano-emulsions (150 mL) were freshly prepared from a PL solution in squalene (typically 1 mg PL/mL squalene) [25,26]. In optimisation studies, we used different water fractions (1, 3, 5 and 10% w/o v/v) for a fixed lipid composition (DPPC/DOTAP (1:1 mol:mol).…”

“…We hypothesised that the self-arrangement of the lipids would affect stability due to the presence of unsaturated bonds, headgroup size and electrostatic interactions. According to Hildebrandt et al [25], there are large differences between, for example, POPC and DPPC at water-squalene interfaces. The disparities in area per molecule and critical aggregation concentration between different PCs were attributed to fatty acid saturation, where the presence of the double bond in oleoyl chain in POPC led to higher attractive (p-p) interactions between unsaturated oil phase and unsaturated fatty acids of POPC and less attractive interactions between saturated fatty acids chains of DPPC and squalene [25].…”

Bioinspired Nanoemulsions Stabilized by Phosphoethanolamine and Phosphoglycerol Lipids

“…In the presence of squalene as dispersion medium, moving the probing group down along the acyl chains, S immediately decreases but then tends to stabilize, maintaining in the case of 14-PCSL a higher value than observed using dodecane as the oil. This is most likely caused by the insertion of the bulky and sterically hindered squalene molecules among the lipid tail termini, which leads to a decrease in the chain termini mobility [ 41 ]. However, because of its molecular structure, squalene is not able to be enter into the monolayer interior.…”